Our FRET studies showing that ERB-041 was the only compound that did not produce any conformational change in ERα at 1 µM demonstrated that ERB-041 is a selective ERβ binder.
We found that ERB-041, LIQ and MF101 were the most ERβ-selective, followed by NYA, and DPN.
Recently, the authors have found out that ERB-hRNase is inhibited by RI, but the level that this IR reaches in the cytosol neutralizes RI [49].
Microarray data demonstrated that ERB-041, MF101 and liquiritigenin were the most ERβ-selective agonists compared to estradiol, followed by nyasol and then diarylpropionitrile.
This indicated that Erb-hcAb and Herceptin have additive effects on growth inhibition through apoptosis.
It should be noted that Erb-hcAb, as reported above, was prepared instead in CHO cells, a mammalian model certainly closer than yeast to human cells.
It has been reported that Erb-hcAb is capable of selective binding to malignant ErbB2-positive cells and of inhibiting their growth in vitro and in vivo, with no effects on ErbB2-negative cells.
We found that Erb-hcAb inhibited the growth of tumours during the course of treatment, and its effects were significantly more potent than that of trastuzumab (75 vs 30% growth inhibition; P-value 0.033).
Because the specific activity of hErb-hRNase, that is the monomeric anti-ErbB2 immunoRNase, previously tested, is 950±25 units nmol 1 (De Lorenzo et al, 2004a), we can conclude that Erb-hcAb-RNase retains about 80% of the activity of the first generation ImmunoRNase.
